This renewal of our NIH U54 SCCPIR Center at the University of California, San Francisco proposes a transdisciplinary, team science approach to elucidate mechanisms underlying seminal events in early development as they relate to the origins and biological consequences of human infertility. Our investigators focus on the developmental continuum from oocyte competence to embryo and placental development to implantation and promote a shared vision of excellence and innovation in reproductive research, advanced technologies, informatics data analyses, mentoring, and community engagement. We combine powerful experimental techniques, system approaches and computational analyses to address critical questions at the intersection of stem cell biology, epigenomics, and clinical reproductive medicine. To accomplish these goals, we have proposed four highly interactive projects by established investigators and one pilot project with a new investigator, which are supported by three cores. Project I (Marco Conti) focuses on mechanisms controlling oocyte developmental competence and early embryo development; Project II (Susan Fisher) will investigate a molecular analysis of the early stages of trophoblast differentiation; Project III (Robert Blelloch) focuses on post-transcriptional regulation of trophoblast differentiation; Project IV (Linda Giudice) will investigate development of human endometrium for embryonic implantation; and the Pilot Project (Nam Tran) proposes to investigate molecular mechanisms underlying the pathogenesis and pathophysiology of endometriosis, a common disorder in women associated with infertility and poor pregnancy outcomes These projects are supported by Core A for administration (Linda Giudice), Core B for computational biology research (Jun Song), and Core C for education and community outreach (Synthia Mellon). Our long-term goals are to understand mechanisms underlying normal and abnormal early development fundamentally and for developing novel strategies to diagnose, prevent and treat infertility; optimize fertility and pregnancy outcomes and minimize adverse outcomes; educate aspiring students, the public, health care professionals and patients about human development and disorders associated with abnormal development; and inspire career choice and nurture career development in this important area of reproductive health and research. These goals are consistent with the mission of the NICHD.